The ability to run selective reactions in biological relevant conditions is a key requirement for biorthogonal chemistry. A number of reactions have been developed in this regard. One of the earliest to be developed in this field was the Bertozzi-Staudinger ligation. The exquisite selectivity of the reagent for azides has led to its wide utilization. The traceless Staudinger modification enhances the non-perturbing nature of this probing strategy by not incorporating the bulky phosphine reagent in the final ligation product. However, aqueous solubility, purification, and synthetic challenges with modifications are some of the limitations with this strategy.<br/><br/>Here we report a one pot synthesis of a modular traceless Staudinger reagent. The incorporation of a clickable handle allows for a high yield functionalization of the reagent for rapid modification. The use of a one pot strategy and a protected phosphine significantly reduces the synthetic challenges associated with functionalized phosphine synthesis. The utility of the strategy is demonstrated by functionalizing the reagent with a purification moiety, water solubilizing group, and a quencher moiety. The relative synthetic ease and functionalizability increases accessibility and opens the opportunity for wider application of the traceless Staudinger strategy in chemical biology.

Synthesis of a modular traceless Staudinger reagent

251st National Meeting (2016)

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